This proposal seeks to identify the factors which modify hepatic RNA synthesis during Q fever in the guinea pig. We will test a tentative model which correlates the observed increased levels of cyclic AMP and cortisol; induction and increased activities of ornithine decarboxylase and S-adenosyl methionine decarboxylase and concomitant increased concentrations of the polyamines putrescine, spermidine and spermine; and the increased activities of RNA polymerases. Catalytic concentrations of the polyamines will be reacted with RNA polymerases, and with (protein kinases + NHCP + ATP) in the presence and absence of cAMP, in searching for a role of polyamines in regulation of RNA synthesis. We will compare the phosphorylated and non-phosphorylated non-histone chromatin proteins (P-NHCP and NHCP) from pre-infected infected and convalescing animals, and attempt to determine whether P-NHCP increase RNA synthesis by interaction with chromatin DNA template, thus making available previously inactive initiation sites. cAMP-dependent and -independent protein kinase activities will be studied during infection using NHCP as well as histone substrates. Nucleoplasmic phoshatases will be studied during infection to see whether the action of phosphatases on P-NHCP reduce polymerase activity, thus modulating transcription. Purified chromatin will be prepared from uninfected and infected livers, and will be dissociated into the DNA, histone, P-NHCP and NHCP fractions. The DNA's will be tested for template activity with purified RNA polymerases from normal and infected liver nuclei. Chromatin will be reconstituted using combinations of fractions from the dissociated "infected" and "uninfected" chromatin. The template properties of the hybrid chromatins will be tested with purified RNA polymerases from normal and infected liver nuclei. Identification of modulating factors of transcription in Q fever may aid in explaining modified transcription which occurs in other types of infectious and noninfectious diseases.